Porous solid materials are widely utilized in the synthesis and purification of organic and biochemicals. For example, the synthesis of biochemicals such as oligonucleotides and polypeptides can be done using solid phase supports in order to greatly reduce the time and expense arising from the inevitable purifications needed between intermediate steps in a multi-step chemical synthesis. The practice of solid phase synthesis is also particularly amenable to automation, thus allowing significant cost-savings in terms of labor. These advantages have prompted a great deal of research activity directed to improvements in solid phase synthesis, and one area of keen interest is the development of superior solid supports.
Many different solid supports are currently used commercially for separation or solid phase synthesis, and many more have been described in various patents and publications. In general, the efficiency of a solid phase synthesis and separation processes depends on the surface area of the solid phase material. Porous materials offer the advantage of higher surface area per unit volume than the corresponding full density solids, permitting vastly improved synthesis and separation performance per unit volume of solid material.
One popular solid support is made from glass or silica, typically in the form of beads. Glass beads have several desirable properties. For example, they are inert to most (although not all) chemical reactions, and they are not easily crushed. Glass has many surface hydroxyl groups that can be used as "chemical handles" to join molecular fragments to the glass. Glass is fundamentally inexpensive, and technology has developed that can make glass beads highly porous, so that the beads have a high surface area/volume ratio.
However, glass beads are also rather brittle, and thus not very stable to mechanical action. When placed into a container with a mechanical stirrer, small pieces of the beads typically chip away, and these small pieces (commonly termed "fines") may find their way into the filtration equipment that is used to separate the beads from the spent reaction solutions. These fines can clog the filtration equipment, and thus present a continuing maintenance problem.
Although there are a large number of organic polymers, in the form of beads, membranes or monoliths, that are not brittle, thereby providing researchers with a potential means for solving the "fines" problem associated with glass beads, identifying an organic-based solid support with the correct balance of properties has proven to be a significant challenge. Typical methods to functionalize an organic polymer, i.e., provide the "chemical handles" that are needed to allow the polymer to serve as a solid-phase synthesis support or chromatography media, are rather harsh and lead to undesirable degradation of the polymer.
There is thus a need in the art for solid-phase supports for synthesis and separations which overcome the disadvantages of the prior art materials. The present invention fulfills this need and provides further related advantages as described herein.